The possible of role phospholipases A2 as inducers of cell and tissue injury in lung is under study. PLA2s purified from polymorphonuclear leukocytes, alveolar macrophages, and human platelets are applied to isolated, perfused lung as is endotoxin and the distribution of lung PLA2s and organelle marker enzymes is determined. Endotoxin (LD25) moderately increased the absolute levels of PLA2 in subcellular fractions from perfused lungs; however no change in subcellular distribution nor specific activity in a given fraction was noted. Hydrolysis of liposomes of phosphatidylethanolamine by PMN-PLA2 was calcium-dependent, but was inhibited by higher concentrations of Ca 2 ion (greater than 2.5 mM) due to alterations of zeta potential of the substrate liposome; thus demonstrating an electrokinetic requirement of the enzyme. PLA2s of the PMN, macrophage, and platelet, and all subcellular fractions of lung were inhibited by the non-steroidal anti-inflammatory agent, indomethacin. In all cases, approximately 5x10-4 M drug concentrations gave 50% inhibition.